Neurobiology of Mental Illness
Questions from each lecture
Lecture 1 – Intro
Why is a diagnoses of a mental illness so difficult?
The requirements of diagnoses of many mental illnesses rely on the use of self-report
questionnaires. This can be unreliable for a number of reasons, for example, the patient may lie
about their condition to make it seem better/worse. As well as this, results of the questionnaire may
vary from day to day whether a patient is experiencing a triggering day or if they are reasonably well.
Terminology within the questionnaire can also be subjective and each patient may interpret it
differently.
Clinicians can also be inconsistent both within themselves and between different clinicians. For
example, a clinician who has been working with an individual with very severe, chronic depression
may find someone with less severe depression as not depressed, in comparison to their more severe
cases. Clinicians may be more experienced in some areas than others. Also, a number of mental
illnesses show significant overlap in symptoms such as schizotypal personality disorder and
schizophrenia. Therefore, it can be difficult for clinicians to disentangle these. The issue of
comorbidity also means that it can be hard to recognise separate disorders occurring at the same
time, and a combination of symptoms from two disorders may present similar to another, different
disorder. In mental illness, there is not usually a particular biomarker or trigger that can be a definite
indicator. PTSD is the only mental illness that presents after one specific life event, so this can be
diagnosed fairly reliably.
What’s a biomarker?
A biomarker, or biological marker, is an indicator of a biological state. It is a characteristic that is
objectively measured and evaluated as an indicator of normal biological processes, pathogenic
processes, or pharmacologic or responses to a therapeutic intervention.
Why are matched controls so important?
It is important to use matched controls in a number of experimental designs in order to have an
accurate comparison for the target group. Controls should be matched on demographics such as
age, gender and race. A good control group also may account for comorbidities. For example, for
research into conduct disorder (which is often comorbid with ADHD), it would be important to have
an ADHD only group as well as a healthy control to compare the CD group to. Therefore, any
differences between the CD and healthy group that are not accounted for by ADHD can be seen, and
the disorders can be differentiated.
What’s the difference between a structural versus a function study? What are the two
types of functional studies?
Structural studies such as MRI or PET scans look into structures within the brain and their volumes,
size, integrity or number of receptors. They may investigate the structural connections between
certain areas. On the other hand, functional studies such as fMRI or EEG look at brain activations i.e.
the areas that are active during particular tasks or what activations correlate with each other and
appear to be functionally connected. Functional studies tend to take resting state and task-related
measures.
, Resting state is useful to see if the brain looks different when it is ‘resting’ and acts as a good
comparison to see what changes during a task. However, it is argued that nobody is ever truly
thinking about nothing, the brain is always active so is it truly a ‘resting’ state? Task-related studies
may be needed to probe the brain to search for differences and compare how a healthy population
may perform differently to a clinical population. However, this also has issues as some say it may
lack construct validity, in that coming up with an appropriate, valid task is difficult. Certain tasks may
lead to ceiling or floor effects.
Group differences, what are they good for?
They are important to show how certain populations may differ to one another.
Lecture 2 – OCD
What is the key circuit that’s hypothesized under scrutiny in OCD?
They key circuit hypothesised to explain neural mechanisms behind OCD is the cortico-thalamic-
cortical circuit. This circuit has a direct and an indirect route. In individuals without OCD, the indirect
route is often take to result in a lower signal being sent back to the orbitofrontal cortex from the
thalamus. However, in OCD, it is hypothesised that the threshold for the direct pathway is lower and
therefore this is stimulated more often compared to in healthy individuals. This direct pathway
results in a larger, excitatory response being sent back to the OFC. It is suggested that this over
activity in the OFC leads to exaggerated concerns about danger and perceived threats (obsessions).
This circuitry is useful in explaining how obsessions can arise, however it does not explain why OCD
patients may be more likely to use the direct pathway or how reinforcement from compulsions acts
upon this system.
On the other hand, this hypothesis does have supporting research from a number of studies, such as
that by Atmaca and colleagues (2007). This research found greater left and right thalamus volumes
in OCD patients when compared to healthy controls. This supports the hypothesis as it could imply
these patients have an overactive thalamus, as implicated by this circuitry. They also noted that the
volume of the thalamus and the OFC correlated with Y-BOCS scores, suggesting that patient’s
severity of symptoms increases with these volumes, or conversely, that these volumes increase with
symptoms. The relationship is correlational therefore we cannot determine causality. **
What are some key structural differences between OCD brain and the healthy brain?
**answered above
What are some key connectivity differences?
fMRI studies reveal differences in connectivity when comparing OCD patients to healthy controls.
Harrison et al (2013) investigated the influence of major OCD symptoms on the corticostriatal
system. They examined resting-state activity in the fMRI scanner and found that patients showed
higher connectivity between the ventral striatum and the OFC, which was predictive of the severity
of OCD symptoms; whereby more severe symptoms correlated with connectivity between striatum
and frontal cortex.
What are some tasks used to study the brain activity of OCD patients?
Research by Olvet et al (2008) looked at event-related negativity (ERN): an event-related negative
event-related potential (ERP) that peaks after an error. It is thought to reflect processing from the
anterior cingulate cortex to inform individuals of a mistake. An example of this would be an arrow
Questions from each lecture
Lecture 1 – Intro
Why is a diagnoses of a mental illness so difficult?
The requirements of diagnoses of many mental illnesses rely on the use of self-report
questionnaires. This can be unreliable for a number of reasons, for example, the patient may lie
about their condition to make it seem better/worse. As well as this, results of the questionnaire may
vary from day to day whether a patient is experiencing a triggering day or if they are reasonably well.
Terminology within the questionnaire can also be subjective and each patient may interpret it
differently.
Clinicians can also be inconsistent both within themselves and between different clinicians. For
example, a clinician who has been working with an individual with very severe, chronic depression
may find someone with less severe depression as not depressed, in comparison to their more severe
cases. Clinicians may be more experienced in some areas than others. Also, a number of mental
illnesses show significant overlap in symptoms such as schizotypal personality disorder and
schizophrenia. Therefore, it can be difficult for clinicians to disentangle these. The issue of
comorbidity also means that it can be hard to recognise separate disorders occurring at the same
time, and a combination of symptoms from two disorders may present similar to another, different
disorder. In mental illness, there is not usually a particular biomarker or trigger that can be a definite
indicator. PTSD is the only mental illness that presents after one specific life event, so this can be
diagnosed fairly reliably.
What’s a biomarker?
A biomarker, or biological marker, is an indicator of a biological state. It is a characteristic that is
objectively measured and evaluated as an indicator of normal biological processes, pathogenic
processes, or pharmacologic or responses to a therapeutic intervention.
Why are matched controls so important?
It is important to use matched controls in a number of experimental designs in order to have an
accurate comparison for the target group. Controls should be matched on demographics such as
age, gender and race. A good control group also may account for comorbidities. For example, for
research into conduct disorder (which is often comorbid with ADHD), it would be important to have
an ADHD only group as well as a healthy control to compare the CD group to. Therefore, any
differences between the CD and healthy group that are not accounted for by ADHD can be seen, and
the disorders can be differentiated.
What’s the difference between a structural versus a function study? What are the two
types of functional studies?
Structural studies such as MRI or PET scans look into structures within the brain and their volumes,
size, integrity or number of receptors. They may investigate the structural connections between
certain areas. On the other hand, functional studies such as fMRI or EEG look at brain activations i.e.
the areas that are active during particular tasks or what activations correlate with each other and
appear to be functionally connected. Functional studies tend to take resting state and task-related
measures.
, Resting state is useful to see if the brain looks different when it is ‘resting’ and acts as a good
comparison to see what changes during a task. However, it is argued that nobody is ever truly
thinking about nothing, the brain is always active so is it truly a ‘resting’ state? Task-related studies
may be needed to probe the brain to search for differences and compare how a healthy population
may perform differently to a clinical population. However, this also has issues as some say it may
lack construct validity, in that coming up with an appropriate, valid task is difficult. Certain tasks may
lead to ceiling or floor effects.
Group differences, what are they good for?
They are important to show how certain populations may differ to one another.
Lecture 2 – OCD
What is the key circuit that’s hypothesized under scrutiny in OCD?
They key circuit hypothesised to explain neural mechanisms behind OCD is the cortico-thalamic-
cortical circuit. This circuit has a direct and an indirect route. In individuals without OCD, the indirect
route is often take to result in a lower signal being sent back to the orbitofrontal cortex from the
thalamus. However, in OCD, it is hypothesised that the threshold for the direct pathway is lower and
therefore this is stimulated more often compared to in healthy individuals. This direct pathway
results in a larger, excitatory response being sent back to the OFC. It is suggested that this over
activity in the OFC leads to exaggerated concerns about danger and perceived threats (obsessions).
This circuitry is useful in explaining how obsessions can arise, however it does not explain why OCD
patients may be more likely to use the direct pathway or how reinforcement from compulsions acts
upon this system.
On the other hand, this hypothesis does have supporting research from a number of studies, such as
that by Atmaca and colleagues (2007). This research found greater left and right thalamus volumes
in OCD patients when compared to healthy controls. This supports the hypothesis as it could imply
these patients have an overactive thalamus, as implicated by this circuitry. They also noted that the
volume of the thalamus and the OFC correlated with Y-BOCS scores, suggesting that patient’s
severity of symptoms increases with these volumes, or conversely, that these volumes increase with
symptoms. The relationship is correlational therefore we cannot determine causality. **
What are some key structural differences between OCD brain and the healthy brain?
**answered above
What are some key connectivity differences?
fMRI studies reveal differences in connectivity when comparing OCD patients to healthy controls.
Harrison et al (2013) investigated the influence of major OCD symptoms on the corticostriatal
system. They examined resting-state activity in the fMRI scanner and found that patients showed
higher connectivity between the ventral striatum and the OFC, which was predictive of the severity
of OCD symptoms; whereby more severe symptoms correlated with connectivity between striatum
and frontal cortex.
What are some tasks used to study the brain activity of OCD patients?
Research by Olvet et al (2008) looked at event-related negativity (ERN): an event-related negative
event-related potential (ERP) that peaks after an error. It is thought to reflect processing from the
anterior cingulate cortex to inform individuals of a mistake. An example of this would be an arrow
